Project description:Recombinant RhCMV was created to study super-infection of Rhesus macaques. These viruses (RhCMV Î178;RhCMV Î182-189;RhCMV Î178Î182-189) were co-hybridized with a wild-type BAC-derived RhCMV to a RhCMV tiling array to ensure that there were no additional mutations beyond the intended deleted regions. Comparison of wild-type BAC-derived RhCMV Î178, RhCMV Î182-189, and RhCMV Î178Î182-189
Project description:Recombinant RhCMV was created to study super-infection of Rhesus macaques. These viruses (RhCMV Δ178;RhCMV Δ182-189;RhCMV Δ178Δ182-189) were co-hybridized with a wild-type BAC-derived RhCMV to a RhCMV tiling array to ensure that there were no additional mutations beyond the intended deleted regions.
Project description:Strain 68-1–derived Rhesus Cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) proteins (RhCMV/SIV) are able to elicit and maintain cellular immune responses that stringently control and subsequently clear a mucosal challenge with highly pathogenic SIV in 50-60% of vaccinated rhesus monkeys (RMs). Here, we utilize whole blood transcriptomic profiling to identify host responses correlated to RhCMV/SIV efficacy.
Project description:Rhesus macaques vaccinated by rhesus cytomegalovirus vectors expressing simian immunodeficiency virus proteins (RhCMV/SIV) activate gene expression signature associated with IL15. To examine the gene expression signature activated by IL15, we performed longitudinal examinations of rhesus macaques during IL15 treament.
Project description:Cytomegalovirus (CMV) is the most common congenital infection worldwide, causing deafness and neurodevelopmental delay in infected infants. Preexisting maternal immunity to CMV is known to influence the incidence and severity of congenital infection. To establish the role of maternal antibody in protection against placental CMV transmission, 6 rhesus CMV (RhCMV)-seronegative rhesus monkey dams were CD4+ T cell depleted at the end of the first trimester of pregnancy and treated with either a single dose of standardly-produced hyperimmune globulin (HIG) (n=3) or a dose-optimized regimen of a potently-neutralizing HIG (n=3) prior to IV inoculation with a mixture of RhCMV strains. Passive infusion with HIG provided complete protection against fetal loss (0/6 HIG-treated vs. 5/6 control dams aborted; p=0.015). Furthermore, the dose-optimized, highly-neutralizing HIG product reduced the magnitude and diversity of maternal plasma RhCMV populations and inhibited placental transmission of RhCMV (0/3 transmitted), suggesting that pre-existing highly-neutralizing antibodies are sufficient to prevent congenital CMV infection and disease. In this study, we sought to investigate the placental transcriptome to determine whether: a) RhCMV congenital infection was being controlled at the level of the placenta, b) what genes are up-regulated following RhCMV congenital infection, and c) whether there are any genes associated with protection against viral infection.
Project description:The 68-1 rhesus cytomegalovirus (RhCMV) vector which expresses Simian Immunodeficiency Virus (SIV) genes (Gag/Tat/Nef/5-Pol) is effective in controlling and clearing SIV in rhesus macaques and the human ortholog vector is a vaccine candidate for the prevention of HIV. Currently the RhCMV/SIV vaccine is only effective in ~55% (referred to as protected animals) of Rhesus Macaques. A previous study by Barrenäs et al., 2021, showed that significant gene expression changes in a key set of IL-15 linked genes was correlated with a protection outcome. To further our understanding of the transcriptomic state if cells in protected animals and mechanisms of protection induced by the RhCMV vaccine we performed single cell RNA-sequencing on PBMCs from protected, non-protected and unvaccinated animals at longitudinal time points post SIV challenge. We identified monocytes, CD8 T cells and NK cells were primarily responsible for expression of genes in the IL-15 enriched protective signature. Myeloid cells were transcriptionally distinct 1) from all other cell types, 2) between nonprotected and protected vaccinated RMs and 3) between protected and unvaccinated SIV-infected animals. Specifically, transcriptomics indicated that myeloid cells were more activated and mature in protected animals by the vaccine at pre-challenge and post-challenge time points. This suggests that the transcriptional state of myeloid cells is essential in eliciting a protection outcome and could be used to determine whether an animal will be protected after vaccination.
Project description:This bulk RNA-seq experiment is designed to uncover the transcriptomic response to modified RhCMV vectors in whole blood of rhesus macaques
Project description:This bulk RNA-seq experiment is designed to uncover the transcriptomic response to modified RhCMV vectors in whole blood of female rhesus macaques
